RESUMO
AIMS/HYPOTHESIS: Our objective was to examine the trends in prepregnancy BMI and glycaemic control among Finnish type 1 diabetic patients and their relation to delivery mode and perinatal outcome. METHODS: We analysed the obstetric records of 881 type 1 diabetic women with a singleton childbirth during 1989-2008. Maternal prepregnancy weight and height were obtained from the maternity cards, where they are recorded as reported by the mother. RESULTS: Maternal BMI increased significantly during 1989-2008 (p < 0.001). The mean HbA(1c) in the first trimester remained unchanged, but the midpregnancy and the last HbA(1c) before delivery increased (p = 0.009 and 0.005, respectively). Elective Caesarean sections (CS) decreased (p for trend <0.001), while emergency CS increased (p for trend <0.001). The mean umbilical artery (UA) pH decreased in vaginal deliveries (p for trend <0.001). The frequency of UA pH <7.15 and <7.05 increased (p for trend <0.001 and 0.008, respectively). The macrosomia rate remained at 32-40%. Neonatal intensive care unit (NICU) admissions increased (p for trend 0.03) and neonatal hypoglycaemia frequency decreased (p for trend 0.001). In multiple logistic regression analysis, maternal BMI was associated with macrosomia and NICU admission. The last HbA(1c) value before delivery was associated with delivery before 37 weeks' gestation, UA pH <7.15, 1 min Apgar score <7, macrosomia, NICU admission and neonatal hypoglycaemia. CONCLUSIONS/INTERPRETATION: Self-reported pregestational BMI has increased and glycaemic control during the second half of pregnancy has deteriorated. Poor glycaemic control seems to be associated with the observed increases in adverse obstetric and perinatal outcomes.
Assuntos
Glicemia/metabolismo , Índice de Massa Corporal , Diabetes Mellitus Tipo 1/epidemiologia , Macrossomia Fetal/epidemiologia , Hemoglobinas Glicadas/metabolismo , Gravidez em Diabéticas/epidemiologia , Adulto , Peso ao Nascer , Cesárea/estatística & dados numéricos , Parto Obstétrico/estatística & dados numéricos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Macrossomia Fetal/sangue , Macrossomia Fetal/fisiopatologia , Finlândia/epidemiologia , Seguimentos , Humanos , Recém-Nascido , Idade Materna , Mães , Gravidez , Resultado da Gravidez , Gravidez em Diabéticas/sangue , Gravidez em Diabéticas/fisiopatologia , Artérias Umbilicais/fisiopatologia , População BrancaRESUMO
OBJECTIVES: A placebo-controlled, randomized, double-blind study was performed to determine whether prenatal dexamethasone (DEX) treatment improves the outcome of the preterm infant when exogenous surfactant is available. METHODS: 157 pregnant women at five hospitals with threatened preterm delivery and with lengths of gestation < 32 weeks received either DEX (dose 6 mg four times at 12-hour intervals) or placebo (PL). Prenatal treatment was not repeated. Preterm infants received rescue therapy of human surfactant (maximum four doses) if they required ventilatory support and at least 40% oxygen for the treatment of respiratory distress syndrome (RDS). RESULTS: Enrolled pregnant women delivered 188 live-born neonates, of whom 79 (DEX 41 and PL 38 neonates) were born 1 to 14 days after the prenatal treatment. Neonates born within 1 to 14 days after the initial DEX treatment had a lower incidence of RDS (DEX, 44%; PL, 79%; P < .01), lower requirements of surfactant (DEX, 22%; PL, 53%; P < .01), shorter duration of ventilatory support (DEX, 2.0 days; PL, 5.3 days; P < .05) and oxygen therapy (DEX, 2.0 days; PL, 7.0 days; P < .01), and a higher neonatal survival without ventilatory support (P < .05) than PL-treated neonates. DEX-treated neonates had higher mean blood pressure than PL-treated neonates during the first 3 days after birth. Among all neonates treated with DEX, there was a lower incidence of intraventricular hemorrhage or periventricular leucomalacia (DEX, 13%; PL, 33%; P < .01). Reduction in the incidence of intraventricular hemorrhage or periventricular leucomalacia in DEX-treated neonates was particularly associated with exogenous human surfactant therapy (DEX+surfactant 10%; PL+surfactant 48%; P < .01). CONCLUSIONS: Prenatal DEX treatment combined with exogenous human surfactant therapy in preterm infants decreases pulmonary morbidity and cerebral complications, and increases survival without severe morbidity.
Assuntos
Hemorragia Cerebral/prevenção & controle , Dexametasona/uso terapêutico , Pneumopatias/prevenção & controle , Cuidado Pré-Natal , Surfactantes Pulmonares/uso terapêutico , Síndrome do Desconforto Respiratório do Recém-Nascido/prevenção & controle , Doença Crônica , Método Duplo-Cego , Feminino , Humanos , Mortalidade Infantil , Recém-Nascido , Recém-Nascido Prematuro , Trabalho de Parto Prematuro , Gravidez , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológicoRESUMO
BACKGROUND: Weekly repeated antenatal corticosteroid treatment improves respiratory outcome but decreases fetal growth and may impair neurodevelopmental outcome. We have previously reported that a single repeat betamethasone (BM) dose neither decreased fetal growth nor improved the outcome of preterm infants during the first hospitalisation. OBJECTIVE: To study prospectively whether a single repeat dose of BM influences neurodevelopment and growth within 2 years. DESIGN: Women with imminent delivery before 34.0 gestational weeks were eligible if they remained undelivered for >7 days after a single course of antenatal BM. After stratification, a single repeat dose of BM (12 mg) or placebo was given. The children underwent neurological and psychometric examinations and a speech evaluation at a corrected age of 2 years. SETTING: Prospective, blinded evaluation following the randomised multicentre trial. PATIENTS: 259 (82%) surviving infants completed the 2-year follow-up, 120 in the BM group and 139 in the placebo group. RESULTS: The rate of survival without severe neurodevelopmental impairment was similar in both groups (BM 98%, placebo 99%). The risk of cerebral palsy (BM 2%, placebo 1%), growth or re-hospitalisation rates (BM 60%, placebo 50%) did not differ between the groups. CONCLUSIONS: A single repeat dose of antenatal BM tended not to influence physical growth or neurodevelopment at 2 years of age.
Assuntos
Betametasona/administração & dosagem , Desenvolvimento Infantil/efeitos dos fármacos , Deficiências do Desenvolvimento/induzido quimicamente , Glucocorticoides/administração & dosagem , Doenças do Prematuro/prevenção & controle , Adulto , Betametasona/efeitos adversos , Pré-Escolar , Esquema de Medicação , Feminino , Seguimentos , Glucocorticoides/efeitos adversos , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Gravidez , Terceiro Trimestre da Gravidez , Nascimento Prematuro/tratamento farmacológico , Cuidado Pré-Natal/métodos , Estudos Prospectivos , Adulto JovemRESUMO
To explain some of the effects of prenatal glucocorticoid treatment on lung function, surfactant parameters in the airway specimens of ventilator-dependent preterm infants were analyzed. In this double-blind study, the mothers of these infants had received dexamethasone (DEX) or placebo prenatally. Human surfactant was given for the treatment of moderate to severe respiratory distress syndrome. Seventy-six preterm infants with mean gestational age of 29 wk and mean birth weight of 1137 g were studied. The concentrations of surfactant components in epithelial lining fluid (ELF) were analyzed, and the surface activity was measured using a pulsating bubble method. Prenatal DEX treatment increased the responsiveness to exogenous surfactant and decreased the severity of respiratory failure during the first day of life. The treatment had no effect on the concentrations of surfactant phospholipids that were generally high. Prenatal DEX treatment increased the association between phospholipid concentration in ELF and the degree of respiratory failure. Prenatal DEX improved the surface activity of surfactant isolated from airway specimens and tended to increase the ratio of surfactant protein A to phosphatidylcholine among recipients of exogenous surfactant. A subgroup of infants, offspring of mothers with severe hypertension had an abnormally low concentration of surfactant protein A and a poor outcome, despite prenatal DEX treatment or surfactant substitution. Prenatal DEX decreased the concentration of nonsedimentable proteins in ELF and decreased the inhibition of surface activity by these proteins. Our results indicate that improved surfactant function during the first day of life explains some of the beneficial pulmonary effects of prenatal glucocorticoid treatment in preterm infants who are ventilator-dependent.
Assuntos
Dexametasona/farmacologia , Glucocorticoides/farmacologia , Cuidado Pré-Natal , Proteínas Associadas a Surfactantes Pulmonares , Surfactantes Pulmonares/uso terapêutico , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Apoproteínas/metabolismo , Método Duplo-Cego , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/genética , Recém-Nascido , Estudos Multicêntricos como Assunto , Fosfatidilcolinas/metabolismo , Gravidez , Surfactantes Pulmonares/metabolismo , Síndrome do Desconforto Respiratório do Recém-Nascido/fisiopatologia , Resultado do TratamentoRESUMO
A randomised double blind placebo controlled study was conducted to determine whether a one week course of dexamethasone could reduce the severity of bronchopulmonary dysplasia in preterm infants without compromising their adrenal function. Forty one infants with a mean birth weight of 880 g and a gestational age of 27 weeks who were ventilator dependent at 10 days of age were enrolled. At the age of 28 days pulmonary outcome was significantly better in the girls treated with dexamethasone but not in all infants. There was no difference between the groups in the long term outcome, except for a shorter duration of supplemental oxygen in dexamethasone treated female infants. After the one week dexamethasone treatment there was a significant but short lived suppression of the basal cortisol concentrations and the adrenal response to corticotrophin (ACTH). No serious side effects were observed. It is concluded that early one week dexamethasone treatment improves short term pulmonary outcome in premature infants, but there is no clear evidence of long term benefits.
Assuntos
Displasia Broncopulmonar/tratamento farmacológico , Dexametasona/uso terapêutico , Recém-Nascido Prematuro , Displasia Broncopulmonar/sangue , Feminino , Humanos , Hidrocortisona/sangue , Recém-Nascido , Masculino , Fatores Sexuais , Fatores de Tempo , Resultado do TratamentoRESUMO
The mechanisms explaining the beneficial effects of glucocorticoid in ventilator-dependent preterm infants are not known. In the present randomized trial, we evaluated the hypothesis that dexamethasone (DEX) treatment of small, preterm infants at risk for chronic lung disease favorably affects the surfactant system. Twenty-three ventilator-dependent infants, with a mean +/- SD gestational age of 26 +/- 2 wk and a mean birth weight of 836 +/- 173 g, received 1 wk of treatment with either DEX (dose 0.5 mg/kg/d) or placebo beginning at 2 wk of age. The airway specimens were analyzed for surfactant components, surface activity, surfactant inhibitors, and inflammatory mediators. The concentrations of these parameters in epithelial lining fluid were calculated using the urea method. DEX treatment decreased the concentration of nonsedimentable protein in epithelial lining fluid within 3 d (p < 0.05). The nonsedimentable fraction of airway specimens decreased the surface activity of surfactant as a function of protein concentration. At a constant protein concentration, the protein from placebo-treated infants inhibited the surface activity of human surfactant in vitro more than protein from DEX-treated infants (p < 0.05). DEX transiently increased the concentration of surfactant protein-A in epithelial lining fluid but had no effect on surface activity of the sedimentable surfactant complex or on concentrations of phosphatidylcholine, IL-1 beta, lactoferrin, or myeloperoxidase. We conclude that the acute beneficial effect of DEX treatment in preterm ventilator-dependent infants may in part be mediated through a decrease in the concentration of non-sedimentable protein and a decrease in the capacity of this protein to inhibit surface activity.
Assuntos
Dexametasona/uso terapêutico , Doenças do Prematuro/tratamento farmacológico , Pneumopatias/tratamento farmacológico , Proteínas Sanguíneas/metabolismo , Doença Crônica , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Doenças do Prematuro/metabolismo , Inflamação/metabolismo , Interleucina-1/metabolismo , Lactoferrina/metabolismo , Pneumopatias/metabolismo , Masculino , Peroxidase/metabolismo , Surfactantes Pulmonares/antagonistas & inibidores , Surfactantes Pulmonares/química , Fatores de Risco , Traqueia/metabolismo , Resultado do TratamentoRESUMO
Our aim was to assess adrenocortical function in very low birth weight infants, specifically to evaluate the impact of gestational age and dexamethasone (DEX) therapy on serum concentrations of total and free cortisol, dehydroepiandrosterone sulfate (DHEAS), and steroid-binding globulins. Twelve moderately preterm or full-term neonates of 38 +/- 4 (mean +/- SD) wk of gestation and 36 ill preterm neonates of 26 +/- 2 (mean +/- SD) wk of gestation were studied. Twenty-three of the 36 ill preterm neonates participated in a randomized neonatal DEX trial for the treatment of early chronic lung disease and received a 1-wk treatment of DEX or placebo. Serum concentrations of cortisol, corticosteroid-binding globulin (CBG), sex hormone-binding globulin (SHBG), and DHEAS were measured, and an ACTH test was performed. Gestational age correlated with the umbilical cord concentrations of total cortisol (r = 0.702, p < 0.01), free cortisol (r = 0.489, p < 0.05), DHEAS (r = 0.608, p < 0.01), and SHBG (r = 0.831, p < 0.01), but not significantly with the concentration of CBG (r = 0.428, p = 0.076). One-week DEX therapy decreased the serum concentrations of CBG (DEX 295 nmol/L, placebo 504 nmol/L; p < 0.01), DHEAS (DEX 6.5 mumol/L, placebo 11.8 mumol/L; p < 0.05), and the basal (DEX 81 nmol/L, placebo 176 nmol/L; p < 0.01) and ACTH-stimulated cortisol levels (DEX 458 nmol/L, placebo 817 nmol/L; p < 0.05). One week after discontinuation of DEX or placebo, basal cortisol concentrations did not differ significantly, but ACTH-stimulated cortisol levels were lower in the DEX-treated than in the placebo-treated infants. DEX therapy decreased the serum CBG and DHEAS concentrations and caused a transient suppression in the adrenocortical function. Despite severe illness, the very preterm neonates had relatively low basal cortisol concentrations, suggesting their reduced ability to respond adequately to stress during intensive care.
Assuntos
Córtex Suprarrenal/fisiologia , Sulfato de Desidroepiandrosterona/sangue , Dexametasona/uso terapêutico , Hidrocortisona/sangue , Recém-Nascido Prematuro/fisiologia , Recém-Nascido de muito Baixo Peso/fisiologia , Doença Crônica , Estudos de Avaliação como Assunto , Idade Gestacional , Globulinas/metabolismo , Humanos , Recém-Nascido , Pneumopatias/tratamento farmacológico , Ligação Proteica , Esteroides/metabolismoRESUMO
AIM: To evaluate the long-term effects of postnatal dexamethasone treatment in high-risk infants of very low birthweight. METHODS: The study included 16 children aged 7.8 to 9.2 y who had been born very prematurely at gestational ages of 24-29 wk and with birthweights of < 1500 g and who had participated in a randomized study of dexamethasone or placebo treatment in ventilator-dependent infants at 10 d of age. Flow-volume spirometry, impulse oscillometry, skin-prick tests and Doppler echocardiography were carried out at school age, and respiratory morbidity and overall neurological outcome evaluated. Controls were 18 non-atopic children born at term, tested for lung function. RESULTS: No significant differences were found in respiratory morbidity at school age between the dexamethasone (n = 8) and placebo (n = 8) groups. Six of the 16 children had moderate to severe neurosensory impairments, but all were able to walk without support and attended primary school. In prematurely born children, standardized height was significantly less than that in controls, but between the two study groups, no significant differences existed in somatic growth. Atopy was uncommon: skin-prick tests were positive in only one child in the placebo group. In the dexamethasone group, forced vital capacity adjusted to height was significantly higher than that in the placebo group, but impairment of basic lung function and bronchial obstruction was evident in both study groups. No hypertrophic cardiomyopathy was apparent, and non-invasive measurements of pulmonary arterial pressure did not reveal any significant difference between the study groups. CONCLUSION: In very low-birthweight children, high respiratory morbidity and neurological impairment continued until school age. Neonatal dexamethasone treatment at school age was not associated with any detectable adverse effects on somatic growth, or pulmonary or cardiac function.
Assuntos
Anti-Inflamatórios/uso terapêutico , Dexametasona/uso terapêutico , Doenças do Prematuro/tratamento farmacológico , Pneumopatias/tratamento farmacológico , Criança , Doença Crônica , Seguimentos , Testes de Função Cardíaca , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Testes de Função Respiratória , Resultado do TratamentoRESUMO
AIMS/HYPOTHESIS: In this study we investigated whether chronic fetal hypoxia, as indicated by amniotic fluid erythropoietin levels, is associated with perinatal morbidity in type 1 diabetic pregnancies. METHODS: A total of 331 women with type 1 diabetes had at least one childbirth between 1995 and 2000. The amniotic fluid erythropoietin concentration was measured in 156 diabetic singleton pregnancies at a median time of 1 day before Caesarean section without labour contractions and in 19 healthy control subjects at Caesarean section. RESULTS: The median amniotic fluid erythropoietin level was 14.0 mU/ml (range 2.0-1975.0) in diabetic pregnancies and 6.3 mU/ml (range 1.7-13.7) in controls (p<0.0001). Of the 156 diabetic patients, 21 (13.5%) had amniotic fluid erythropoietin levels higher than 63.0 mU/ml. Amniotic fluid erythropoietin levels correlated negatively with umbilical artery pH (r=-0.49, p<0.0001) and pO2 (r=-0.62, p<0.0001) at birth and neonatal lowest blood glucose level (r=-0.47, p<0.0001). Positive correlations were found between amniotic fluid erythropoietin levels and umbilical artery pCO2 (r=0.49, p<0.0001) and last maternal HbA1c (r=0.43, p<0.0001). Furthermore, a U-shaped correlation was demonstrated between amniotic fluid erythropoietin levels and birthweight z score (z score below -0.6 SD units: r=-0.63, p=0.0007; z score above +1.0 SD units: r=0.32, p=0.0014). Neonatal hypoglycaemia, hypertrophic cardiomyopathy and admission to the neonatal intensive care unit occurred significantly more often in cases with high amniotic fluid erythropoietin levels (>63.0 mU/ml) than in those with normal levels. Multivariate logistic regression analysis revealed that amniotic fluid erythropoietin was the only variable independently related to low umbilical artery pH (<7.21; p<0.0001) and neonatal hypoglycaemia (p=0.002). Low umbilical artery pO2 (<15.0 mm Hg) was explained by amniotic fluid erythropoietin (p<0.0001) and birthweight z score (p=0.004). CONCLUSIONS/INTERPRETATION: Antenatal high amniotic fluid erythropoietin levels can identify type 1 diabetic pregnancies at increased risk of severe perinatal complications.